The NIH-sponsored Training Program in Investigative Rheumatology, begun at Yale in 1976, has the philosophy that a portion of biomedical scientists, both M.D.s and Ph.D.s, should be trained in an environment that focuses upon mechanisms of rheumatologic and immunologic diseases, and approaches to the bedside investigation of these illnesses. This belief is grounded in the notion that the challenges involve in understanding these clinical problems requires a cohort of investigators whose knowledge and training enable them to span the gaps between basic biology, clinical investigation, and clinical rheumatology and immunology. Hence, the goals of this program are to attract individuals who are interested in learning about fundamental mechanisms of disease and the applications of this knowledge, and to provide trainees with the foundation in basic and clinical science that will enable them to bridge the differences between bench research and clinical medicine, and to approach rheumatologic problems at the bedside. Thus, the program is focused upon clinical investigation in the rheumatic diseases, with an emphasis on providing fundamental training in immunology, cellular and molecular biology, and the clinical sciences, as applied to the understanding and therapy of rheumatic diseases; is comprised of MD, MD/PhD and PhD trainees; and has for its training faculty a collaborative group of 29 physician and basic scientists from the Section of Rheumatology and other Sections in the Department of Medicine, and investigators from the Department of Immunobiology. The quality, cohesiveness, and skills of these mentors, along with the skills and the desire of the trainees, are the most important requisites for success of the program. Five trainees (MD and PhD) per year are currently supported, with that number requested in this renewal. This request is based upon the success of the program and the number of high quality applicants. MD trainees typically perform clinical work in the first year of their fellowship (supported by clinical funds), and then enter research training, often enrolling in Masters' or PhD degree- granting programs while supported by this grant. Research training for both MD and PhD fellows typically encompasses at least two to three years, or in some cases longer, with later years in training, following support from this Training Grant, aided by individual fellowship grants and research career development awards. The combination of both MD and PhD fellows gives the former a better research experience, and it exposes the latter to opportunities to apply their skills to rheumatologic problems. Fellows supported by this Training Grant receive didactic as well as interactive instruction in biology, research techniques, and ethical issues in science. This program provides trainees with the foundation in basic and clinical sciences that will enable them to bridge the differences between basic research and fundamental approaches to understanding rheumatic diseases.